부산대학교 도서관

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease, and cysts), monoallelic loss-of-function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2genes. Herein, we report 6 non-family-related cases of monoallelic IFT140LoF variants, identified from 1,340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140presented with several bilateral cysts, revealed after kidney imaging, and was found to carry a pathologic frameshift IFT140variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 also exhibited dilated cardiomyopathy, which was of unknown origin, as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140and heart disease.